Turning genes on to turn cancer off  pg. 2

Vidaza and Dacogen are now joined by a lengthy list of DNA methylation inhibitors and chromatin-modifying drugs that are in preclinical and clinical testing. Chromatin is the DNA-histone protein complex.

“We’re just beginning this era of epigenetic drugs,” Jones says.

DNA methylation and other epigenetic “biomarkers” may also be useful for early cancer detection, diagnosis, and prognosis.

Wael El-Rifai, M.D., Ph.D., and colleagues at the Vanderbilt-Ingram Cancer Center have noted DNA hypermethylation of several genes in Barrett’s esophagus—a change in the cells lining the esophagus that can progress to esophageal adenocarcinoma. The frequency of hypermethylation increases as the cells progress from Barrett’s esophagus to dysplasia (pre-cancerous condition) to adenocarcinoma.

“Promoter DNA hypermethylation is an early change in tumorigenesis, and it’s a progressive one,” says El-Rifai, professor of Surgery and Cancer Biology.

It’s now time, Jones and other contend, to engage in a Human Epigenome Project, an effort to identify and understand all of the chemical tags that coordinate expression of genes.

“It’s critically important that we understand the human epigenome: it’s at the heart of what stem cells are, it’s an essential component of aging, and it’s of major importance in human diseases, particularly cancer,” Jones says. “We’re going ahead full speed.”

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